Musculoskeletal Diseases comprise the most frequent ailment for primary care physician visits in the United States, and the increases in incidence of musculoskeletal diseases with aging (particularly osteoporosis and osteoarthritis) is higher in women than in men, and leads to a significant amount of disability and reduced quality of life. Epidemiologic data clearly demonstrate the proportion of women affected my musculoskeletal diseases is higher than in men with aging, yet the biologic explanation for this sex difference remains unclear. The objective of this interdisciplinary, multi-institutional proposal, entitled Sex Differences in Musculoskeletal Conditions Across the Lifespan, is to integrate cutting-edge basic science regarding sex differences in the physiology relate to acquiring peak bone mass, epidemiologic study on the relation of sex differences in bone shape to occurrence, severity and prognosis of osteoarthritis, clinical study of sex differences in high resolution ultrasound in diagnosis and prognosis of carpal tunnel syndrome with conservative and surgical treatment, and a randomized trial of sex differences in response to a physical activity intervention for kyphosis. The overarching goal of this Specialized Center of Research is to inform and transform preventive efforts and clinical practice in diagnosis and treatment of these musculoskeletal conditions in both sexes and lead to improvements in women's health. The four projects that compose the Center will conduct critical, innovative research to characterize sex differences in musculoskeletal conditions via: 1) a mechanistic study of sex differences in progesterone receptors that are related to regulation or influence peak bone mass, 2) a prospective clinical cohort study using novel diagnostic technology to examine sex differences in the results of this technology to diagnose carpal tunnel syndrome and sex differences in standard treatments for this condition, 3) an epidemiologic imaging study to assess sex differences in bone shape and the influence of bone shape on the development, severity and prognosis of osteoarthritis of the knee, and 4) a randomized clinical trial of sex differences in response to an exercise intervention for the treatment of kyphosis. The Center's research results will be translated to the local and national medical community's through presentations by Center researchers at a number of different forums, including UC Davis and UCSF continuing medical education programs, as well as local grand rounds and national meetings. PUBLIC HEALTH REFERENCE: This translational SCOR grant, Sex Differences in Musculoskeletal Diseases Across the Lifespan, focuses on four musculoskeletal diseases or syndromes that differ by sex and include peak bone mass (a laboratory based project), carpal tunnel syndrome (epidemiologic and observational), osteoarthritis of the knee (observational), and kyphosis (exercise intervention). Each project will carefully determine the sex differences in relation to the musculoskeletal diseases and inform preventive and clinical practices.